Hydrogels have been adopted as tools for the study of many diverse types of biological phenomena and in applications such as tissue engineering, biological sensors and microarrays, protein and polymer purification, and drug delivery. They are composed mostly of water and maintain their self-supporting and elastic nature by a network of hydrophilic polymers that are chemically, physically, and/or ionically cross-linked, leading to a material that swells in the presence of water and that can yield mechanical and/or chemical properties similar to those of biological tissues. Polymers of synthetic and natural origins have been exploited for the above applications including poly(ethylene glycol) (PEG), poly(vinyl alcohol), poly(N-isopropylacrylamide), gelatin, collagen, and alginate, and hyaluronic acid, with the application dictating the structural requirement of the chosen polymer.
Heparin, a highly sulfated and variable glycosaminoglycan, is a well-known biomolecule and widely employed anticoagulant in subcutaneous and intravenous therapies, although currently not in a long-term hydrogel delivery format. The anionic character of heparin mediates binding to numerous proteins which in turn mediates many cell fate processes including cell proliferation, differentiation and control of chemokine signaling.
In hydrogels developed for drug delivery, one mode of degradation or release can rely on the reduction of disulfide bonds by glutathione (GSH), a reducing agent found naturally in circulation and cellular compartments. Typically, the extracellular concentration of GSH is relatively low in plasma (ca. 1-20 μM) and relatively high in cells (ca. 0.5-10 mM), providing a level of stability for conjugates and hydrogels outside the cell and aiding in rapid degradation of disulfides intracellularly.
The ability to control degradation in heparin-containing polymeric hydrogels based on PEG, hyaluronic acid, or other polymeric matrices as drug delivery platforms, tissue engineering scaffolds, and related polymeric materials has potential for programmed temporal, spatial, and targeted control of degradation for in vitro cellular studies and future clinical application. Therefore, the development of compositions which permit tunable control over degradation in vivo so as to release a drug or other bioactive molecule according to a particular desired profile or in response to particular physiological conditions would therefore be of great interest.